The quadrupole ion trap invented by Paul and Steinwedel (Paul, W. and H. Steinwedel (1960) U.S. Pat. No. 2,939,952) is a highly versatile and sensitive mass spectrometer. An important analytical use of quadrupole ion trap mass spectrometers is tandem mass spectrometry (MS/MS).
The fundamentals and operation of MS/MS on the quadrupole ion trap mass spectrometer have been previously described (March, R. E. et al. Eds. (1989) Quadrupole Storage Mass Spectrometry (John Wiley & Sons, New York); March, R. E., et al. Eds. (1995) Practical Aspects of Ion Trap Mass Spectrometry v.I-III (CRC Press, New York); and Johnson, J. V. et al. (1990 ) Anal. Chem. 62:2162). During MS/MS, daughter ions (also called product ions) are produced by first isolating the parent ion (also called the precursor ion) and then causing the parent ion to undergo collision-induced dissociation (CID). In the ion trap, CID is produced by applying a resonant excitation waveform, for example, across the endcap electrodes. Parent ions which have a secular frequency of oscillation corresponding to the frequency of the applied resonant excitation waveform gain kinetic energy and, therefore, the amplitudes of their orbits increase. Specifically, since an ion's secular frequency is a function of that ion's mass-to-charge ratio (m/z), ions of only a small range of m/z will gain kinetic energy for a given excitation frequency. Thereafter, CID occurs as these resonantly excited ions undergo fragmentation upon colliding with a buffer gas, for example, helium which is present in the ion trap.
Current versions of commercially available quadrupole ion trap mass spectrometers which are capable of tandem mass spectrometry (MS/MS) are limited to resonantly exciting and dissociating ions of a single m/z or ions within a small m/z range. This limits the ion trap to performing only daughter ion MS/MS experiments. Specifically, the current versions of the Finnigan MAT GCQ.TM. and LCQ.TM. quadrupole ion trap mass spectrometer are able to isolate a single m/z ion (the parent ion) and fragment it to produce daughter ions which can be resonantly ejected from the ion trap, using a mass-selective instability scan, and subsequently detected. However, there are two other very useful types of MS/MS scan modes, namely, parent and neutral loss scans, also called precursor scans and constant neutral loss scans. Both of these scan modes are useful for screening samples for the presence of particular analytes. In particular, parent scans are useful for screening for classes of compounds whose parent ions fragment to a common and characteristic daughter ion, and neutral loss scans are useful for screening for classes of compounds whose parent ions fragment upon CID to form daughter ions via loss of a common neutral fragment.
A technique was previously described for performing parent and neutral loss experiments on the quadrupole ion trap (Johnson, J. V. et al. (1991) U.S. Pat. No. 5,075,547). The Johnson et al. (1991) disclosure employed a sequential pulsing of resonant excitation waveforms of appropriate frequency and voltage to sequentially fragment several parent ion (m/z)'s and determine if each produced the particular daughter ion m/z of interest. There are several limitations to using the Johnson et al. (1991) technique for practical screening of analytical samples. First, because the RF voltage applied to the ring electrode was held constant while each of the different parent (m/z)'s were fragmented, CID was performed at a different q.sub.z for each parent m/z (q.sub.z .varies.RF Voltage/(m/z)). Since the efficiency of CID is known to vary with q.sub.z, this results in different analysis sensitivities for the different (m/z)'s of the parent ions. Second, daughter ions of different (m/z)'s were detected using resonant ejection with the RF voltage constant. Since daughter (m/z)'s are resonantly ejected at different q.sub.z 's, both mass resolution and detection efficiency are dependent on the m/z of the daughter ion. In addition, standard mass calibration which is used for conventional mass analysis cannot be used, requiring an extra calibration procedure. Finally, no method of determining which parent ion (m/z)'s will be fragmented is given, meaning the operator must know which parent ion (m/z)'s are being interrogated. However, the parent (m/z)'s which will be present in a sample is usually not known a priori.
Another technique was previously described for performing parent and neutral loss experiments on the quadrupole ion trap (Johnson, J. V. et al. (1992) U.S. Pat. No. 5,171,991). The Johnson et al. (1992) disclosure employed the simultaneous application of two resonant excitation voltages or waveforms across the endcap electrodes. First, a daughter ion resonant excitation waveform, corresponding to the secular frequency of the characteristic daughter ions, is applied to cause rapid resonant excitation and ejection of any characteristic daughter ions through an opening in an exit endcap, whereby the characteristic daughter ions can then be detected. After any characteristic daughter ions in the trap have been ejected and while still applying the characteristic daughter ion resonant excitation waveform, a parent ion resonant excitation waveform, corresponding to the secular frequency of the parent ion of interest, is applied, at an appropriate voltage to induce CID of the parent ions with minimal ejection of the parent ions from the trap. A positive result for a given m/z parent ion occurs when CID of that parent ion produces the characteristic daughter ion which is ejected and detected. However, even though the Johnson et al. (1992) disclosure allows for a fast scan over all relevant parent ion m/z, when the parent ions undergo CID there can be some parent ions which are resonantly ejected. These ions can be detected and produce false positive readings for the detection of the characteristic daughter ions. Also, when the parent ions undergo CID three can be some daughter ions produced which are too low in m/z to be stable within the ion trap and are therefore ejected. This can result in false positive readings for the detection of the characteristic daughter ions. Any of these or other false positive readings are unacceptable for most applications.